Outcomes to 5 years of outborn versus inborn infants <32 weeks in Western Australia: a cohort study of infants born between 2005 and 2018.

OBJECTIVE: We compared mortality and morbidity of inborn versus outborn very preterm infants <32 weeks' gestation in Western Australia (WA) between 2005 and 2018. DESIGN: Retrospective cohort study. PATIENTS: Infants <32 weeks' gestation who were born in WA. MAIN OUTCOME MEASURES: Mortality was assessed as death before discharge home from the tertiary neonatal intensive care unit. Short-term morbidities included combined brain injury (intracranial haemorrhage grade ≥3 and cystic periventricular leukomalacia) and other major neonatal outcomes. Developmental assessments at age 2, 3 and 5 years were evaluated. We performed multivariable logistic regression analysis of outborn status on outcomes, controlling for gestational age, birth weight z-score, sex and multiple birth. RESULTS: A total of 4974 infants were born in WA between 22 and 32 weeks' gestation between 2005 and 2018 of which 4237 (89.6%) were inborn and 443 (10.4%) were outborn. Overall mortality to discharge was higher in outborn infants (20.5% (91/443) vs 7.4% (314/4237); adjusted OR (aOR) 2.44, 95% CI 1.60 to 3.70, p<0.001). Outborn infants had higher rates of combined brain injury than those inborn (10.7% (41/384) vs 6.0% (246/4115); aOR 1.98, 95% CI 1.37 to 2.86), p<0.001). No difference in up to 5-year developmental measures was detected. Follow-up data were available for 65% of outborn and 79% of inborn infants. CONCLUSIONS: Outborn preterm infants <32 weeks in WA had increased odds of mortality and combined brain injury than those inborn. Developmental outcomes up to 5 years were similar between groups. Loss to follow-up may have impacted the long-term comparison.

When and how do patients with cardiac amyloidosis die?

BACKGROUND: Cardiac amyloidosis (CA) is an underappreciated cause of morbidity and mortality. Light-chain (AL) and transthyretin (ATTR) amyloidosis have different disease trajectories. No data are available on subtype-specific modes of death (MOD) in patients with CA. METHODS AND RESULTS: We retrospectively investigated 66 with AL and 48 with wild-type ATTR amyloidosis (ATTRwt) from 2000 to 2018. ATTRwt differed from AL by age (74.6 ± 5.4 years vs. 63 ± 10.8 years), posterior wall thickness (16.8 ± 3.3 mm vs. 14.3 ± 2.2 mm), left ventricular mass index (180.7 ± 63.2 g/m2 vs. 133.5 ± 42.2 g/m2), and the proportions of male gender (91.7% vs. 59.1%), atrial enlargement (92% vs. 68.2%) and atrial fibrillation (50% vs. 12.1%). In AL NYHA Functional Class and proteinuria (72.7% vs. 39.6%) were greater; mean arterial pressure (84.4 ± 13.5 mmHg vs. 90.0 ± 11.3 mmHg) was lower. Unadjusted 5-year mortality rate was 65% in AL-CA vs. 44% in the ATTRwt group. Individuals with AL-CA were 2.28 times ([95%CI 1.27-4.10]; p = 0.006) more likely to die than were individuals with ATTRwt-CA. Information on MOD was available in 56 (94.9%) of 59 deceased patients. MOD was cardiovascular in 40 (66.8%) and non-cardiovascular in 16 (27.1%) patients. Cardiovascular [28 (68.3%) vs. 13 (80%)] death events were distributed equally between AL and ATTRwt (p = 0.51). CONCLUSION: Our data indicate no differences in MOD between patients with AL and ATTRwt cardiac amyloidosis despite significant differences in clinical presentation and disease progression. Cardiovascular events account for more than two-thirds of fatal casualties in both groups.

[Unusual coincidence of partially active endocrine tumors]. / Ungewöhnliche Häufung von partiell endokrin aktiven Tumoren.

We report on a female patient who developed five different tumors between the age of 53 and 62 years. The following tumors were diagnosed, three of which showed endocrine activity: uterine myoma; hemangiopericytoma of the meninges; pleural mesothelioma; preperitoneal leiomyoma; medullary carcinoma of the thyroid (sporadic form) in a hyperthyroid goiter. Coexistence of hyperthyroidism and medullary carcinoma of the thyroid is rare. Paraneoplastically induced hypoglycemia--in this patient induced by the pleural mesothelioma and less by the preperitoneal leiomyoma--is of similarly infrequent occurrence. Tumors of epithelial or mesenchymal origin may cause hypoglycemia as a result of peptide secretion, exerting an insulin-like effect. The detection of IGF-I and IGF-II in the serum confirms the diagnosis. Insulinoma can be differentiated by the absence of hyperinsulinemia.

Electrophysiologic effects of intravenous aminophylline in heart transplant recipients with sinus node dysfunction.

BACKGROUND: Sinus node dysfunction has been reported to occur in up to 50% of orthotopic heart transplant recipients, and oral theophylline has been used in an attempt to limit the morbidity associated with this abnormality. The purpose of this study was to evaluate the electrophysiologic effects of methylxanthines on sinus node function. METHODS: Sinus node testing performed in 26 patients before and after the infusion of 6 mg/kg of aminophylline. Thirteen of these patients had abnormal sinus node function at baseline, and thirteen had normal sinus node function. Sinus node dysfunction was diagnosed by a rhythm other than sinus in five patients, a prolonged corrected sinus node recovery time in two patients, and the presence of a secondary pause in six patients. RESULTS: In patients with abnormal sinus node function a significant decrease was observed in the sinus node recovery time (-14% +/- 5%) and corrected sinus node recovery time (-33% +/- 25%) in response to aminophylline; however, neither parameter was normalized. A decrease in the sinus cycle length (-6% +/- 8%) was not statistically significant. In patients with normal sinus node function, a significant decrease was seen in both the sinus node recovery time (-9% +/- 7%) and sinus cycle length (-9% +/- 4%). The corrected sinus node recovery time decreased by 4% +/- 28% in patients with normal conditions but was not significant. Overall, aminophylline resolved the underlying sinus node abnormality in only one of thirteen patients with abnormal sinus node function. CONCLUSIONS: This study suggests that the use of theophylline in patients with marked sinus node dysfunction may not decrease their risks for subsequent bradycardic events.

Increased levels of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) correlate with tumor necrosis factor alpha (TNF alpha)-release in patients suffering from microangiopathy following allogeneic bone marrow transplantation (BMT).

Severe microangiopathy resembling thrombotic thrombocytopenic purpura (TTP) has been reported as a complication of acute graft-versus-host disease (aGvHD) in patients receiving cyclosporin (CsA) prophylaxis following allogeneic BMT. In order to analyze the pathophysiological events involved in microangiopathy, a prospective study comparing release of von Willebrand Factor (vWF), t-PA and PAI, as well as TNF alpha and further coagulation parameters was performed in 32 patients. Endothelial damage as the central lesion was confirmed by the close association of vWF and t-PA:Antigen with severity of microangiopathy. t-PA activity, however, was neutralized by a simultaneous rise in PAI. Activation of coagulation in the course of microangiopathy was further confirmed by increased levels of DDimer (DDi), fibrinopeptide A (FPA), beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). As clinical grades of microangiopathy, as well as the release of t-PA:Ag and PAI were correlated with systemic release of TNF alpha our data further support our hypothesis of cytokine induced endothelial damage in clinical complications following allogeneic BMT.

Treatment of aGVHD with OKT3: clinical outcome and side-effects associated with release of TNF alpha.

Monoclonal antibodies are increasingly used for treatment of acute graft-versus-host disease (aGVHD) in bone marrow transplantation. We treated seven patients with steroid resistant aGVHD with the monoclonal anti-T cell antibody OKT3. Though five patients showed improvement of aGVHD, only two became long-term survivors. OKT3 treatment was accompanied by deterioration of microangiopathy and prolonged increase of tumor-necrosis-factor alpha serum levels indicating activation of monocytes/macrophages in vivo, as this was not observed in a control group of patients receiving anti-T cell globulin. These findings may be related to immunostimulatory activity reported for OKT3 in vitro. Strategies interfering with cytokine release should improve clinical results of OKT3 treatment.

Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation.

Severe microangiopathy has been reported as a rare complication of cyclosporine A (CsA) prophylaxis in allogeneic bone marrow transplantation (BMT). We found morphological and biochemical changes indicative of generalized endothelial damage in 49 of 66 allogeneic marrow graft recipients receiving cyclosporine, but none in 11 patients treated with methotrexate for prophylaxis of graft-v-host disease (GVHD). Changes occurred after engraftment of bone marrow and consisted of intravascular hemolysis with red cell fragmentation and de novo thrombocytopenia. They were preceded by a decrease in activated partial thromboplastin time and fibrinogen indicating activation of coagulation. Endothelial damage as the central lesion of microangiopathy was confirmed by a simultaneous increase of factor VIII related antigen. Severe microangiopathy was observed in ten patients and was fatal in seven. Risk factor analysis revealed a highly significant association of microangiopathy with severity of acute GVHD (aGVHD) (P less than .001) and use of CsA prophylaxis (P less than .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of a aGVHD, which is not inhibited by CsA prophylaxis.

[Immunologic studies in relation to cryotherapy of gynecologic diseases]. / Immunologische Untersuchungen im Zusammenhang mit der Kryotherapie gynäkologischer Erkrankungen

The interesting nexus of problems related to the behaviour of the T-cell effected immunity situation of patients treated by means of cryosurgery and operations, was commenced by examinations of 118 women in regard of the transformability of lymphocytes. By the help of swab-preparations and especially of the PHA-stimulated lymphocyte transformation test, patients have been controlled in regard of vulva carcinoma, cervix carcinoma, condyloma, kraurosis vulvae and other portio findings being in need for medical attendence. Though the results are not to be regarded without reserve, the cryotherapy seems to improve the T-cell effected immunity situation in some of the patients suffering from vulva carcinoma. Up to now, the controls have also shown that they may reveal prognostic suggestions in certain cases.

Screening, fermentation, isolation, and chracterization of trypanomycin, a new antibiotic.

A Streptomyces strain which is similar to S. diastatochromogenes (Krainsky) Waksman et Henrici 1948 sensu Hütter (1967) was found to produce a new antibiotic designated trypanomycin. The red-pigment antibiotic, which has novel trypanocidal activity in vitro and in vivo, was isolated from a C-, N-, and iron-containing culture of the strain IMET JA 10081/9 by extraction with organic solvents, transfer into the aqueous phase, reextraction with organic solvents at pH 6.8, precipitation by hydrocarbons, and purification by chromatographic methods. Trypanomycin has indicator properties. The main constituents of the antibiotic mixture are readily soluble in water and are very stable in distilled water at room temperature (28 C) for 24 hr. The composition of the base of trypanomycin A(2) (melting point, 175 to 183 C) corresponds to the empirical formula C(41-42)H(52-56)NO(21-22). The absorption spectra in the ultraviolet and visible regions are very similar to those of the 4,5,8-trioxyanthrachinones. Trypanomycin has strong antiprotozoal activity, e.g., against trypanosomes. The natural substance additionally inhibits the growth of gram-positive bacteria, stable as well as unstable L-forms of gram-negative bacteria, mycoplasmas, yeast protoplasts, and tumor cells in vitro. The LD(50) of trypanomycin in mice was 60 mg/kg when administered intravenously and 31 mg/kg on intraperitoneal administration. If the antibiotic was added to cultures of animal or human cells in vitro, mitotic inhibition and chromosomal aberrations resulted. Trypanomycin differs in its biological activities and chromatographic behavior from other anthracyclines, e.g., cinerubine A and B, daunomycin, adriamycin, nogalamycin, rutilantin, pyrromycin, cyclamycin, and ryemycin.